A simultaneous DSC-FTIR microspectroscopy was used to investigate the solid-state characterization of anhydrous glucose (GLU), L-asparagine monohydrate (LAM), and GLU-LAM physical mixture. A conventional DSC and TG analytical methods were also applied. The results indicate that the degradation of GLU was started after complete melting, but LAM was previously dehydrated around 93°C and then degraded beyond the initial melting temperature. Three endothermic peaks at 54, 108 and 123°C were observed in the DSC curve of GLU-LAM physical mixture, which was markedly different from that of the superimposed DSC curves of GLU and LAM, due to the GLU-LAM interaction via possible Maillard reaction. DSC-FTIR microspectroscopic result demonstrates that a continuous-stepwise reaction process was directly evidenced from Schiff base intermediate to Amadori product and then to decarboxylated Amadori product in the interaction of GLU and LAM by this one-step technique. The present study suggests that solid-state reaction between GLU and LAM could be easily detected and directly observed using a unique DSC-FTIR microspectroscopy in real time.